Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

肌球蛋白 1b (Myo1b) 是 I 类肌球蛋白的重要单头膜相关马达，参与​​许多关键的生理和病理过程。越来越多的证据表明，Myo1b 表达失调已在多种肿瘤的发生和发展过程中得到广泛研究。然而，Myo1b 在 CRC 血管生成和自噬进程中的功能机制仍不清楚。在此，我们发现 Myo1b 的表达在 CRC 组织中上调，其高表达与较差的生存相关。Myo1b的过表达促进了CRC细胞的增殖、迁移和侵袭。相反，Myo1b 的沉默抑制了体外和体内的肿瘤进展。进一步的研究表明，Myo1b 抑制自噬体-溶酶体融合并增强 CRC 细胞的 VEGF 分泌以促进血管生成。从机制上讲，Myo1b 阻断 HIF-1α 的自噬降解，然后导致 HIF-1α 的积累，从而增强 VEGF 分泌，进而促进 CRC 中的肿瘤血管生成。总之，我们的研究为 Myo1b 在 CRC 进展中的作用提供了新的见解，并表明它可能是 CRC 患者可行的预测生物标志物和有前途的治疗靶点。